Synergism of As_2S_2 and STI 571 in inducing apoptosis of K562 cells

Objective To investigate the synergistic effect of As_2S_2 and STI 571 on K562 cells and its mechanism. Methods The inhibitive effect of As_2S_2 on the proliferation of K562 cells was determined by cell number count.Cell apoptosis was assessed by flow cytometry, DNA fragmentation and morphology. Protein expression was determined by Western-blot and gene expression by RT-PCR. Results As_2S_2 could significantly inhibit the proliferation and induce apoptosis of K562 cells in a dose and time-dependent manner at concentrations from 1 μmol/L to 5 μmol/L for 24～72 h. 34.4%, 21.8% and 46.0% of the treated-cells displayed apoptosis at 3 μmol/L for 72 h, 5 μmol/L for 48 h and 5 μmol/L for 72 h, respectively. Compared to treatment with STI571 (0.25～1.00 μmol/L) or As_2S_2 (1～5 μmol/L) alone, treatment of K562 cells with As_2S_2 and STI571 combination induced more cell apoptosis. (18.4±1.4)% and (15.8±1.2)% cells underwent apoptosis at 1 μmol/L STI571 for 48 h and 5 μmol/L As_2S_2 for 48 h,respectively, and (40.6±2.0)% cells did in combination treatment ( P 0.05). For U937 cells,the percentages of apoptotic cells were (6.0±1.1)% at 1 μmol/L STI571 for 48 h, (4.5±1.2)% at 5 μmol/L As_2S_2 for 48h, and (7.3±1.0)% in combination treatment. As_2S_2 decreased the bcr-abl fusion protein expression and PTK activity of c-abl and bcr-abl, but not for bcr-abl expression. Conclusion Combination treatment with As_2S_2 and STI 571 induced more apoptosis of K562 cells. The reduction of PTK activity may be involved in the mechanisms.